A tissue when damaged or lost by a disease or injury does not usually recover fully to its original shape. For example, once an alveolar bone is eroded by a periodontal disease, the damaged alveolar bone and periodontal ligament tissue cannot be regenerated because of the excessive growth of connective tissues in the lost part of the bone tissue.
The tissue regeneration methods currently practiced to solve the above problem include a method of autografting and implanting a non-immunogenic animal or human bone, or an artificial bone substitute such as hydroxyapatite or tricalcium phosphate.
Another method which employs various membranes has also been developed to separate tissues at a defect site from the surrounding tissues and to induce regeneration of new tissues within the defect site.
International Patent Publication No. WO 90/11730 discloses a method for regenerating an alveolar bone by using, e.g., expanded polytetrafluoroethylene as a material for separating and reinforcing the alveolar bone tissue. However, in this method, non-degradable materials such as the expanded polytetrafluoroethylene must be removed by a secondary surgical operation, which may cause the infection or inflammation of the operated site.
Accordingly, various implantable articles of bioresorbable polymers have been developed to eliminate the need for secondary surgical operations.
International Patent Publication No. WO 92/10218 discloses a bioresorbable article for the separation and regeneration of tissues at a defect site, which comprises a fibrous material laminarly affixed to one surface of a barrier film. This articles is designed such that the regeneration of the desired tissues can take place in the space created on the fibrous side of the barrier film. The ingrowth of surrounding tissues into the defect site is prevented by keeping the surrounding tissues on the other side of the film.
However, the barrier film obstructs flows of material thereacross; particularly, timely integration of tissues from both sides of the film is hampered. Moreover, the space needed for the propagation of desired tissues can be secured by other means, e.g., by using an article which can be shaped to closely fit against surrounding tissues, thereby creating a space within the treatment site. To prepare such an article, a bioresorbable polymer having good malleability is required.
International Patent Publication No. WO 92/15340 discloses a bioresorbable polymer composition including a plasticizer, e.g., a citrate. The polymer composition is sufficiently malleable for fabricating therefrom an implantable article that is well adaptable to the shape of the treatment site to be covered. WO 92/15340 also specifies that said article should be made of a membrane having double layer structure consisting of a film having a fretted microstructure and another film having round micropores.
The disclosure by WO 92/15340 has a problem in that the plasticizer used in the claimed formulation may increase the risk of inflammation at the site of implantation.
A bioresorbable polymer membrane for use in the separation and regeneration of desired tissues should have a proper balance of the following properties depending on the desired effect of its intended use: (1) biodegradation in vivo, (2) structural or dimensional stability in vivo for a predetermined period, (3) malleability or flexibility, (4) tissue compatibility and adhesion, (5) cell-barrier property and (6) permeability of the extracellular fluid and other materials.
Many of the above properties appear to act counter to each other, e.g., a plasticizer which imparts good malleability may increase tissue inflammation, a fast rate of biodegradation would compromise the structural integrity, a membrane having a good cell-barrier property would also impede the permeabilities of other materials, and vise versa. The membrane of the present invention is advantageous in that: (1) it does not contain any plasticizer which may induce inflammation; (2) biocompatible polymers which are well-known in the art are employed; (3) its fiber matrix imparts good physical properties, e.g., tensile strength and structural stability to the membrane; (4) due to its highly porous structure it has a good flexibility and cell attachment; and (5) it becomes malleable when embossed.